A new class of leukotriene biosynthesis inhibitor: the development of MK-0591.

P Prasit, M Belley, M Blouin, C Brideau, C Chan, S Charleson, J F Evans, R Frenette, J Y Gauthier, J Guay

Index: J. Lipid Mediat. 6(1-3) , 239-44, (1993)

Full Text: HTML

Abstract

The evolution of MK-0591 (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-ylmethoxy+ ++)indol-2-yl]- 2,2-dimethylpropanoic acid), 12, a potent, orally active leukotriene biosynthesis inhibitor is described. MK-0591 is currently undergoing clinical evaluation as a potential agent for the treatment of asthma and inflammatory bowel disease. It acts through a novel mechanism by a specific interaction with a membrane protein, 5-lipoxygenase activating protein (FLAP), which has been shown to be essential for LT synthesis in inflammatory cells. A brief comparison of its biological activity with that of its progenitors MK-886 and L-674,636 is described.